Study reveals that stabilizing a specific protein could help to treat spinal muscular atrophy (SMA), amyotrophic lateral sclerosis (ALS), and possibly other motor neuron diseases. (Cusabio provides SMN and Recombinant HTR1B.)
SMA results from a deficiency of survival motor neuron (SMN) protein due to mutations in the SMN1 gene. The deficiency leads to degeneration of motor neurons and atrophy of skeletal muscle. The severity of disease symptoms varies greatly from individual to individual. Milder forms of SMA can cause movement problems, while more severe forms can cause paralysis and even death. Currently, there is no effective therapy for SMA, and treatment is usually limited to supportive care.
One possible SMA treatment is to fix the disease-causing gene, and previous studies have been mainly focused on this approach. For the new study, the researchers tested an alternative approach in which a therapeutic agent was used to stabilize the SMN protein. The researchers found that a common compound that blocks the degradation of SMN protein improved survival of motor neurons in both human cell cultures and mouse models.
The team found that SMN levels are widely variable in motor neurons, and this phenomenon is seen in motor neurons derived from SMA patients, ALS patients, and controls. This raises the hypothesis that some SMN-elevating drugs might be effective in motor neuron diseases besides SMA.
Importantly, the researchers also found that motor neurons with high SMN are more likely to survive when exposed to toxic environments and stressors, while cells with low SMN are susceptible to cell death. Collectively, the findings indicate that drugs that restore the levels of SMN in motor neurons may prevent cell death.
The researchers treated human and mouse motor neurons with a compound that blocks a process involved in the degradation of SMN protein, and observed that exposure to the compound stabilized SMN proteins and therefore increased SMN levels, which improved motor neuron survival.
Findings of the study have been described in a paper in Cell Reports. Natalia Rodriguez-Muela and Nadia Litterman are co-first author, and Lee Rubin is the corresponding author.
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